Background: Glioblastoma (GBM) remains an incurable disease. Radiotherapy and temozolomide are the backbone of the treatment. Clinical and molecular factors are essential to define prognosis. Methods: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). We perform a prospective evaluation about prognostic factors in GBM patients treated with temozolomide concurrent with and adjuvant to radiotherapy. Results: One hundred sixty-nine GBM patients (median age, 60 years; range 29 – 82) were prospectively evaluated. MGMT methylation status was available in 140 patients. Combining gender and MGMT methylation status we obtained four groups of patients: 36 male pts with methylated MGMT (25.7%), 47 male pts with unmethylated MGMT (33.6%), 32 female pts with methylated MGMT (22.9%), 25 female pts with unmethylated MGMT (17.9%). Results of univariate analysis are summarized in the table 1.Table: M1nmOS95%CImethylated male3116.39.2 -23.4unmethylated male4115.611.8 - 19.5methylated female26nrunmethylated female2117.011.8 - 22.2total11917.015.2 - 18.9 Open table in a new tab Overall survival (OS) was significantly different between methylated male and methylated female (p = 0.028), methylated male and unmethylated female (p = 0.031), unmethylated male and methylated female (p = 0.002), methylated female and unmethylated female (p < 0.001). In multivariate analysis, gender and MGMT methylation considered together (met female vs met male HR = 0.459; 95% CI 0.242 – 0.827; p = 0.017), age (HR 1.025; 95% CI 1.002 – 1.049; p = 0.032) and Karnofsky Performance Status (KPS) (HR 0.965; 95% CI 0.948 – 0.982; p < 0.001) were significantly correlated with OS. Conclusions: The median overall survival is consistently higher for female pts with methylated MGMT, treated with temozolomide concurrent with and adjuvant to radiotherapy. When considered simultaneously with MGMT methylation status, gender might impact on clinical outcome and should be considered as a prognostic factor.